Variant chr5-138753541-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001903.5(CTNNA1):c.-3+31G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00483 in 375,156 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0051 ( 14 hom., cov: 32)

Exomes 𝑓: 0.0046 ( 13 hom. )

Consequence

CTNNA1
NM_001903.5 intron

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0110

Variant links:

Genes affected

CTNNA1 (HGNC:2509): (catenin alpha 1) This gene encodes a member of the catenin family of proteins that play an important role in cell adhesion process by connecting cadherins located on the plasma membrane to the actin filaments inside the cell. The encoded mechanosensing protein contains three vinculin homology domains and undergoes conformational changes in response to cytoskeletal tension, resulting in the reconfiguration of cadherin-actin filament connections. Certain mutations in this gene cause butterfly-shaped pigment dystrophy. [provided by RefSeq, May 2016]

CTNNA1 links:

CTNNA1-AS1 (HGNC:):

CTNNA1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 5-138753541-G-C is Benign according to our data. Variant chr5-138753541-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 223743.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00511 (773/151362) while in subpopulation AMR AF= 0.0295 (449/15224). AF 95% confidence interval is 0.0272. There are 14 homozygotes in gnomad4. There are 385 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 773 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA1	NM_001903.5 linkuse as main transcript	c.-3+31G>C		intron_variant		ENST00000302763.12
CTNNA1-AS1	NR_134244.1 linkuse as main transcript	n.384C>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA1	ENST00000302763.12 linkuse as main transcript	c.-3+31G>C		intron_variant		1	NM_001903.5	P1	P35221-1

Frequencies

GnomAD3 genomes

AF:

0.00511

AC:

773

AN:

151254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000946

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0295

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00326

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00346

Gnomad OTH

AF:

0.00433

GnomAD4 exome

AF:

0.00464

AC:

1039

AN:

223794

Hom.:

Cov.:

AF XY:

0.00448

AC XY:

511

AN XY:

114088

show subpopulations

Gnomad4 AFR exome

AF:

0.00164

Gnomad4 AMR exome

AF:

0.0478

Gnomad4 ASJ exome

AF:

0.000126

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00139

Gnomad4 FIN exome

AF:

0.00493

Gnomad4 NFE exome

AF:

0.00377

Gnomad4 OTH exome

AF:

0.00455

GnomAD4 genome

AF:

0.00511

AC:

773

AN:

151362

Hom.:

Cov.:

AF XY:

0.00520

AC XY:

385

AN XY:

73990

show subpopulations

Gnomad4 AFR

AF:

0.000943

Gnomad4 AMR

AF:

0.0295

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00326

Gnomad4 NFE

AF:

0.00346

Gnomad4 OTH

AF:

0.00428

Alfa

AF:

0.00635

Hom.:

Bravo

AF:

0.00855

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Hereditary cancer-predisposing syndrome

Benign:1

Likely benign, no assertion criteria provided

clinical testing

University of Washington Department of Laboratory Medicine, University of Washington

Dec 01, 2015

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

6.9

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over